Description (Adapted from Application): The long-term goal of this project is to determine how opiates, including some commonly used in drug addiction therapy, affect macrophages, a key cell in immune defenses. This is important because it has been postulated that the susceptibility of drug addicts to infections may be due, at least in part, to suppressive effects of opiates on important components of the immune system Recent observations in this laboratory show that the effect of morphine on phagocytosis by macrophages is dependent on the concentration of the drug and conditions of exposure: acute exposures are inhibitory, whereas chronic exposure leads to a putative tolerant/dependent state. The investigators plan to extend their observations and study the effect of morphine on respiratory burst activity (RB) and NO (nitric oxide) production. Effects on RB will be measured by flow cytometry, and NO production will be determined using the Griess reagent. They also plan to test the effect on these processes, including phagocytosis, of opiates used in drug addiction therapy, such as methadone, L-alpha-acetyl-methadol (LAAM) and buprenorphine. This will provide information about any possible deleterious effects that these drugs may have on the immune system of the addict. Finally, they plan to initiate studies on the effect of morphine, methadone, LAAM and bupremorphine on phagocytosis by human monocytes. Monocytes will be obtained from both control donors and HIV- methadone patients with known medical history. This will allow them to determine if the observations on murine macrophages are of relevance to understand the possible role of opiates in the immunosuppression observed in drug addicts.